Translocation method of sclareolide

Abstract

The invention provides a transposition method of sclareolide. The transposition method comprises the following steps: carrying out configuration conversion reaction on raw materials comprising sclareolide reactants and a first catalyst to obtain a sclareolide product with configuration (c); wherein the sclareolide reactant comprises sclareolide of a configuration (a) and / or sclareolide of a configuration (b); wherein the chemical structures of sclareolide of the configuration (a), sclareolide of the configuration (b) and sclareolide of the configuration (c) are respectively as follows: # imgabs0 # first catalyst comprises Lewis base. According to the method, common and easily available Lewis base is used as a catalyst, sclareolide of a configuration (a) and sclareolide of a configuration (b) are subjected to configuration conversion reaction, and the selectivity of sclareolide of a configuration (c) is higher, so that the yield of sclareolide of the configuration (c) is increased.

Description

Technical Field

[0001] The present invention relates to the technical field of sclareolide, and in particular, to a method for the rearrangement of sclareolide. Background Art

[0002] Sclareolide is mainly used in the synthesis of natural ambergris substitutes and is also used in the blending of fragrances in smaller amounts. Sclareolide is an excellent tobacco flavor enhancer. In blended cigarettes, it can mask the harsh odor of tobacco, improve and enhance the quality of the fragrance, impart a pleasant characteristic aroma to the tobacco, make the cigarette softer and smoother on the palate, and is an effective flavor enhancer. Sclareolide can enhance and improve the sensory properties of food, and thus is widely used in the food industry. In foods containing sweet seasonings, sclareolide can be used as a flavoring agent to increase the olfactory effect of the food. Adding a small amount of sclareolide to the coffee industry can intensify the bitterness of coffee to improve the refreshing effect of coffee.

[0003] There are three configurations of sclareolide. The Chinese patent application with the publication number CN112759548A uses sclareolide as the starting material and undergoes a configuration transformation in an environment of sulfuric acid and formic acid. After converting from configuration (a) to configuration (c), the reaction continues to prepare a PAR-1 inhibitor, but its conversion rate and yield are relatively low. Therefore, it is urgent to develop a new method for the rearrangement of sclareolide. Summary of the Invention

[0004] The main object of the present invention is to provide a method for the rearrangement of sclareolide to solve the problem of low configuration conversion rate and yield of sclareolide in the prior art.

[0005] To achieve the above object, according to one aspect of the present invention, a method for the rearrangement of sclareolide is provided. The rearrangement method includes: performing a configuration conversion reaction on a raw material including a sclareolide reactant and a first catalyst to obtain a sclareolide product of configuration (c); wherein the sclareolide reactant includes sclareolide of configuration (a) and / or sclareolide of configuration (b); wherein the chemical structures of sclareolide of configuration (a), sclareolide of configuration (b), and sclareolide of configuration (c) are respectively:

[0006]

[0007] The first catalyst includes a Lewis base.

[0008] Further, the Lewis base is selected from LiOH, NaOH, KOH, Na 2 CO 3 and NaHCO 3any one or more of them; and / or, the first catalyst further includes inorganic salts, and the mass ratio of the Lewis base to the inorganic salts is 5-10:1. The inorganic salts are NaCl and / or KCl; and / or, the mass ratio of the first catalyst to the sclareolide reactant is 1-10:100.

[0009] Further, the raw materials further include a first organic solvent, and the first organic solvent is selected from any one or more of ethanol, propylene glycol, and toluene; and / or, the mass ratio of the sclareolide reactant to the first organic solvent is 1:5-50; and / or, the reaction temperature of the configuration conversion reaction is 70-90°C, and / or, the reaction pressure of the configuration conversion reaction is 1-30 atm, and / or, the reaction time of the configuration conversion reaction is 1-5 h.

[0010] Further, the preparation method of the sclareolide reactant includes: Step S1, successively performing a first mixing, a hydrogenation reaction, and a rough distillation on the raw materials including α,β-unsaturated 4-(2,6,6-trimethyl-1-cyclohexenyl)-2-methylbutenal, a palladium-carbon catalyst, and a sodium hydroxide solution to obtain 4-(2,6,6-trimethyl-1-cyclohexenyl)-2-methylbutyraldehyde; Step S2, successively performing a condensation reaction and a decarboxylation reaction on the raw materials including 4-(2,6,6-trimethyl-1-cyclohexenyl)-2-methylbutyraldehyde, malonic acid, and an amino acid catalyst to obtain (E)-β-monocyclic homofarnesoic acid; Step S3, performing a cyclization reaction on the raw materials including (E)-β-monocyclic homofarnesoic acid and a trifluoroacetic acid catalyst to obtain the sclareolide reactant.

[0011] Further, in the above Step S1, the palladium-carbon catalyst is a 3-5 wt% Pd / C catalyst, and the mass ratio of α,β-unsaturated 4-(2,6,6-trimethyl-1-cyclohexenyl)-2-methylbutenal to the palladium-carbon catalyst is 90-110:1; and / or, the mass ratio of sodium hydroxide to water in the sodium hydroxide solution is 1-3:100.

[0012] Further, the above Step S1 further includes performing a hydrogenation reaction and a rough distillation on the first mixed liquid after the first mixing after gas displacement using a hydrogenation kettle; wherein, nitrogen and hydrogen are used for gas displacement, and the number of gas displacement times is 3-5 times; and / or, during the rough distillation process, the top temperature of the hydrogenation kettle is 100-105°C, and the kettle temperature of the hydrogenation kettle is 120-130°C; and / or, the reaction temperature of the hydrogenation reaction is 60-80°C, the reaction pressure of the hydrogenation reaction is 2.5-3.0 MPa, and the reaction time of the hydrogenation reaction is 3-5 h.

[0013] Further, the above-mentioned step S2 further includes: step S21, subjecting a raw material including 4-(2,6,6-trimethyl-1-cyclohexenyl)-2-methylbutyraldehyde, malonic acid, an amino acid catalyst, a second organic solvent, and a first water remover to a condensation reaction and then performing vacuum distillation to obtain a first reaction solution; step S22, subjecting a raw material including the first reaction solution, a third organic solvent, and a second water remover to a decarboxylation reaction, and then successively performing first washing, first extraction, first vacuum concentration, and first recrystallization to obtain (E)-β-monocyclic homofarnesoic acid; wherein, malonic acid is successively added in the form of first malonic acid, second malonic acid, and third alanine in the condensation reaction, the sum of the total masses of the first malonic acid, the second malonic acid, and the third alanine is equal to the mass of malonic acid, and the mass ratio of the first malonic acid, the second malonic acid, and the third alanine is 1:1-3:3-5.

[0014] Further, the amino acid catalyst is L-proline, the second organic solvent is cyclohexane, and the first water remover is tert-butanol; and / or, the mass ratio of 4-(2,6,6-trimethyl-1-cyclohexenyl)-2-methylbutyraldehyde, malonic acid, and the amino acid catalyst is 20-25:12.4-15:1.12-1.5; the mass ratio of 4-(2,6,6-trimethyl-1-cyclohexenyl)-2-methylbutyraldehyde to the volume of the first water remover is 1.25-1.5 g / mL; and / or, the reaction temperatures of the condensation reaction and the decarboxylation reaction are each independently 80-85 °C, and the reaction times of the condensation reaction and the decarboxylation reaction are each independently 3-4 h; and / or, the third organic solvent is N-methylpyrrolidone, and the second water remover is magnesium chloride; and / or, the mass ratio of the first reaction solution to the second water remover is 100-110:20-25.

[0015] Further, the above-mentioned step S3 further includes: step S31, mixing (E)-β-monocyclic homofarnesoic acid and a fourth organic solvent to obtain an (E)-β-monocyclic homofarnesoic acid solution; step S32, mixing trifluoroacetic acid and a fifth organic solvent to obtain a trifluoroacetic acid solution; step S33, subjecting the (E)-β-monocyclic homofarnesoic acid solution and the trifluoroacetic acid solution to a cyclization reaction to obtain a second reaction solution; step S34, successively performing second extraction, second washing, second vacuum concentration, and second recrystallization on the second reaction solution to obtain a sclareolide reactant.

[0016] Further, the fourth organic solvent and the fifth organic solvent are each independently dichloromethane; and / or, the mass ratio of the (E)-β-monocyclic homofarnesoic acid solution to the trifluoroacetic acid solution is 125-150:405-500; and / or, the temperature of the second reaction solution is -10-0 °C; and / or, the reaction time of the cyclization reaction is 2-3 h.

[0017] Applying the technical solution of the present invention, compared with adding an acidic reagent in the method for the rearrangement of sclareolide, the acidic reagent will be further rearranged into other isomers. In this application, a common and easily available Lewis base is used as a catalyst to carry out a configuration conversion reaction on sclareolide of configuration (a) and sclareolide of configuration (b) to obtain sclareolide of configuration (c). This rearrangement method has a higher selectivity for sclareolide of configuration (c), thereby increasing the yield of sclareolide of configuration (c). In addition, the rearrangement method of this application has the advantages of high conversion rate, short reaction time, high product yield, low product cost, no environmental pollution, and simple post-treatment. BRIEF DESCRIPTION OF THE DRAWINGS

[0018] The accompanying drawings forming a part of this application are used to provide a further understanding of the present invention. The schematic embodiments of the present invention and their descriptions are used to explain the present invention and do not constitute an improper limitation to the present invention. In the drawings:

[0019] Figure 1 The synthesis reaction path diagram of sclareolide of configuration (c) of this application is shown. DETAILED DESCRIPTION OF THE EMBODIMENTS

[0020] It should be noted that, without conflict, the embodiments in this application and the features in the embodiments can be combined with each other. The present invention will be described in detail below with reference to the drawings and in combination with the embodiments.

[0021] As analyzed in the background art of this application, there are problems of low configuration conversion rate and yield of sclareolide in the prior art. To solve the above problems, this application provides a method for the rearrangement of sclareolide.

[0022] In a typical embodiment of this application, a method for the rearrangement of sclareolide is provided. The rearrangement method includes: carrying out a configuration conversion reaction on a raw material including a sclareolide reactant and a first catalyst to obtain a sclareolide product of configuration (c); wherein, the sclareolide reactant includes sclareolide of configuration (a) and / or sclareolide of configuration (b); wherein, the chemical structures of sclareolide of configuration (a), sclareolide of configuration (b), and sclareolide of configuration (c) are respectively:

[0023]

[0024] The first catalyst includes a Lewis base.

[0025] Compared with the addition of an acidic reagent in the method for the rearrangement of sclareolide, the acidic reagent will be further rearranged into other isomers. In this application, a common and easily available Lewis base is used as a catalyst to carry out a configuration conversion reaction on sclareolide of configuration (a) and sclareolide of configuration (b) to obtain sclareolide of configuration (c). This rearrangement method has higher selectivity for sclareolide of configuration (c), thereby increasing the yield of sclareolide of configuration (c). In addition, the rearrangement method of this application has the advantages of high conversion rate, short reaction time, high product yield, low product cost, no environmental pollution, and simple post-treatment.

[0026] In one embodiment of this application, the Lewis base is selected from any one or more of LiOH, NaOH, KOH, Na 2 CO 3 and NaHCO 3 ; and / or, the first catalyst further includes an inorganic salt, and the mass ratio of the Lewis base to the inorganic salt is 5-10:1. The inorganic salt is NaCl and / or KCl; and / or, the mass ratio of the first catalyst to the sclareolide reactant is 1-10:100.

[0027] Preferably, the first catalyst further includes an inorganic salt, and controlling the types of the Lewis base and the inorganic salt and the mass ratio of the Lewis base to the inorganic salt within the above range helps to further adjust the pH value of the solution to provide a buffering effect, thereby accelerating the rearrangement reaction rate. Preferably, the mass ratio of the first catalyst to the sclareolide reactant is within the above range, which helps to further increase the conversion rate and the yield of sclareolide of configuration (c).

[0028] In one embodiment of this application, the raw material further includes a first organic solvent, and the first organic solvent is selected from any one or more of ethanol, propylene glycol, and toluene; and / or, the mass ratio of the sclareolide reactant to the first organic solvent is 1:5-50; and / or, the reaction temperature of the configuration conversion reaction is 70-90°C, and / or, the reaction pressure of the configuration conversion reaction is 1-30 atm, and / or, the reaction time of the configuration conversion reaction is 1-5 h.

[0029] Preferably, the raw material further includes a first organic solvent, and controlling the type of the first organic solvent and the mass ratio of the sclareolide reactant to the first organic solvent within the above range helps to optimize the polarity of the reaction medium and the reaction environment, thereby facilitating the conversion of sclareolide of a specific configuration into the target configuration. Preferably, the reaction temperature, reaction pressure, and reaction time of the configuration conversion reaction are within the above range, which helps to further improve the selectivity of the configuration conversion reaction and the yield and purity of sclareolide of configuration (c) and reduce the generation of by-products.

[0030] In an embodiment of the present application, the preparation method of the sclareolide reactant includes: Step S1, successively performing first mixing, hydrogenation reaction, and rough distillation on raw materials including α,β-unsaturated 4-(2,6,6-trimethyl-1-cyclohexenyl)-2-methylbutenal, palladium-carbon catalyst, and sodium hydroxide solution to obtain 4-(2,6,6-trimethyl-1-cyclohexenyl)-2-methylbutanal; Step S2, successively performing condensation reaction and decarboxylation reaction on raw materials including 4-(2,6,6-trimethyl-1-cyclohexenyl)-2-methylbutanal, malonic acid, and amino acid catalyst to obtain (E)-β-monocyclic homofarnesoic acid; Step S3, performing cyclization reaction on raw materials including (E)-β-monocyclic homofarnesoic acid and trifluoroacetic acid catalyst to obtain the sclareolide reactant.

[0031] In the present application, using α,β-unsaturated 4-(2,6,6-trimethyl-1-cyclohexenyl)-2-methylbutenal as the starting material, through the reaction paths of hydrogenation reaction, condensation reaction, decarboxylation reaction, and cyclization reaction in sequence, a sclareolide reactant including sclareolide of configuration (a), sclareolide of configuration (b), and sclareolide of configuration (c) is obtained. The reaction path of the above preparation method is simple and easy to operate.

[0032] In an embodiment of the present application, in the above Step S1, the palladium-carbon catalyst is a 3-5 wt% Pd / C catalyst, and the mass ratio of α,β-unsaturated 4-(2,6,6-trimethyl-1-cyclohexenyl)-2-methylbutenal to the palladium-carbon catalyst is 90-110:1; and / or, the mass ratio of sodium hydroxide to water in the sodium hydroxide solution is 1-3:100.

[0033] Preferably, the type of the palladium-carbon catalyst and the mass ratio of α,β-unsaturated 4-(2,6,6-trimethyl-1-cyclohexenyl)-2-methylbutenal to the palladium-carbon catalyst are within the above ranges, which helps to improve the efficiency of the subsequent hydrogenation reaction. Preferably, the mass ratio of sodium hydroxide to water in the sodium hydroxide solution is within the above range, which helps α,β-unsaturated 4-(2,6,6-trimethyl-1-cyclohexenyl)-2-methylbutenal and the palladium-carbon catalyst to be better dispersed in the sodium hydroxide solution.

[0034] In an embodiment of the present application, the above Step S1 further includes performing hydrogenation reaction and rough distillation on the first mixed liquid after the first mixing after gas replacement using a hydrogenation kettle; wherein, nitrogen and hydrogen are used for gas replacement, and the number of gas replacement times is 3-5 times; and / or, during the rough distillation process, the top temperature of the hydrogenation kettle is 100-105 °C, and the kettle temperature of the hydrogenation kettle is 120-130 °C; and / or, the reaction temperature of the hydrogenation reaction is 60-80 °C, the reaction pressure of the hydrogenation reaction is 2.5-3.0 MPa, and the reaction time of the hydrogenation reaction is 3-5 h.

[0035] Preferably, gas replacement and the above hydrogenation reaction are carried out in a hydrogenation kettle, and the conditions of the hydrogenation reaction are controlled within the above range, which helps to effectively remove oxygen in the reaction system, avoid side reactions, and at the same time accelerate the hydrogenation reaction, thereby improving the purity and yield of the 4-(2,6,6-trimethyl-1-cyclohexenyl)-2-methylbutyraldehyde product. Preferably, the temperature at the top of the hydrogenation kettle and the kettle temperature during the rough distillation process are controlled within the above range, which helps to further improve the purity of the 4-(2,6,6-trimethyl-1-cyclohexenyl)-2-methylbutyraldehyde product.

[0036] In an embodiment of the present application, the above step S2 further includes: step S21, subjecting a raw material including 4-(2,6,6-trimethyl-1-cyclohexenyl)-2-methylbutyraldehyde, malonic acid, an amino acid catalyst, a second organic solvent, and a first water remover to a condensation reaction and then performing vacuum distillation to obtain a first reaction solution; step S22, subjecting a raw material including the first reaction solution, a third organic solvent, and a second water remover to a decarboxylation reaction, and then successively performing a first washing, a first extraction, a first vacuum concentration, and a first recrystallization to obtain (E)-β-monocyclic homofarnesoic acid; wherein, malonic acid is added successively in the form of a first malonic acid, a second malonic acid, and a third alanine during the condensation reaction, the sum of the total masses of the first malonic acid, the second malonic acid, and the third alanine is equal to the mass of malonic acid, and the mass ratio of the first malonic acid, the second malonic acid, and the third alanine is 1:1-3:3-5.

[0037] Preferably, the above step S2 is used to prepare (E)-β-monocyclic homofarnesoic acid, which helps to improve the reaction efficiency of the condensation reaction and the decarboxylation reaction, thereby improving the yield of (E)-β-monocyclic homofarnesoic acid. Preferably, malonic acid is added successively in the form of a first malonic acid, a second malonic acid, and a third alanine according to the reaction conditions during the condensation reaction, and controlling the mass ratio of the first malonic acid, the second malonic acid, and the third alanine within the above range helps to reduce the malonic acid lost due to thermal decomposition, thereby improving the yield of (E)-β-monocyclic homofarnesoic acid. Preferably, the second organic solvent, the first water remover, and the water generated by the condensation reaction are removed by vacuum distillation. Preferably, an oil bath is used, which helps to control the reaction temperature of the condensation reaction and the decarboxylation reaction, thereby improving the stability of the reaction. Preferably, reflux is used, which helps to improve the reaction efficiency of the condensation reaction and the decarboxylation reaction.

[0038] In one embodiment of the present application, the amino acid catalyst is L-proline, the second organic solvent is cyclohexane, and the first water scavenger is tert-butanol; and / or, the mass ratio of 4-(2,6,6-trimethyl-1-cyclohexen-1-yl)-2-methylbutyraldehyde, malonic acid and the amino acid catalyst is 20-25:12.4-15:1.12-1.5; the mass ratio of 4-(2,6,6-trimethyl-1-cyclohexen-1-yl)-2-methylbutyraldehyde to the volume of the first water scavenger is 1.25-1.5 g / mL; and / or, the reaction temperatures of the condensation reaction and the decarboxylation reaction are each independently 80-85 °C, and the reaction times of the condensation reaction and the decarboxylation reaction are each independently 3-4 h; and / or, the third organic solvent is N-methylpyrrolidone, and the second water scavenger is magnesium chloride; and / or, the mass ratio of the first reaction solution to the second water scavenger is 100-110:20-25.

[0039] Preferably, the type of the amino acid catalyst and the mass ratio of 4-(2,6,6-trimethyl-1-cyclohexen-1-yl)-2-methylbutyraldehyde, malonic acid and the amino acid catalyst are within the above ranges, which helps to further improve the efficiency of the condensation reaction. Preferably, the second organic solvent, the first water scavenger is tert-butanol, and the mass ratio of 4-(2,6,6-trimethyl-1-cyclohexen-1-yl)-2-methylbutyraldehyde to the volume of the first water scavenger are within the above ranges, which helps to remove the water generated in the condensation reaction, thus facilitating the subsequent smooth participation of magnesium chloride in the reaction. Preferably, the type of the second water scavenger and the mass ratio of the first reaction solution to the second water scavenger are within the above ranges, which helps to remove the water generated in the reaction. Preferably, the reaction temperatures and reaction times of the condensation reaction and the decarboxylation reaction are within the above ranges, which helps to improve the yield of (E)-β-monocyclic homofarnesoic acid.

[0040] In one embodiment of the present application, the above step S3 further includes: step S31, mixing (E)-β-monocyclic homofarnesoic acid with a fourth organic solvent to obtain an (E)-β-monocyclic homofarnesoic acid solution; step S32, mixing trifluoroacetic acid with a fifth organic solvent to obtain a trifluoroacetic acid solution; step S33, subjecting the (E)-β-monocyclic homofarnesoic acid solution and the trifluoroacetic acid solution to a cyclization reaction to obtain a second reaction solution; step S34, subjecting the second reaction solution to a second extraction, a second washing, a second reduced pressure concentration and a second recrystallization to obtain the raw material.

[0041] Through the above steps S31 and S32, it helps to better disperse (E)-β-monocyclic homofarnesoic acid and trifluoroacetic acid in the organic solvent, thus facilitating the cyclization reaction of (E)-β-monocyclic homofarnesoic acid under the action of the trifluoroacetic acid catalyst. Through the above step S34, it helps to further improve the conversion rate and yield of sclareolide of configuration (a) and sclareolide of configuration (b).

[0042] In one embodiment of the present application, the fourth organic solvent and the fifth organic solvent are each independently dichloromethane; and / or, the mass ratio of the (E)-β-monocyclic homofarnesoic acid solution to the trifluoroacetic acid solution is 125-150:405-500; and / or, the temperature of the second reaction solution is -10 to 0 °C; and / or, the reaction time of the cyclization reaction is 2-3 h.

[0043] Preferably, controlling the mass ratio of the (E)-β-monocyclic homofarnesoic acid solution to the trifluoroacetic acid solution, the temperature of the second reaction solution, and the reaction time of the cyclization reaction within the above ranges helps to further improve the reaction efficiency of the cyclization reaction, thereby obtaining a sclareolide reactant including sclareolide of configuration (a) and sclareolide of configuration (b).

[0044] The beneficial effects of the present application will be further described below in conjunction with embodiments.

[0045] Example 1

[0046] Preparation of sclareolide reactant: Weigh 0.15 g of sodium hydroxide and dissolve it in 15 g of water to prepare a sodium hydroxide solution. Add 45 g (2.18 mo1) of α,β-unsaturated 4-(2,6,6-trimethyl-1-cyclohexenyl)-2-methylbutenal and 0.6 g of 5 wt% palladium-carbon catalyst Pd / C to the sodium hydroxide solution for the first mixing to obtain a first mixed solution.

[0047] Pump the first mixed solution into a hydrogenation kettle, perform gas replacement 3 times with nitrogen and hydrogen, and then carry out a hydrogenation reaction. The reaction temperature of the hydrogenation reaction is 70 °C, the reaction pressure is 2.5 MPa, the reaction time is 3 h, cool down to room temperature, filter after the reaction, and obtain a crude product of 4-(2,6,6-trimethyl-1-cyclohexenyl)-2-methylbutanal. The crude product is subjected to rough distillation in the hydrogenation kettle to obtain a colorless transparent liquid of 4-(2,6,6-trimethyl-1-cyclohexenyl)-2-methylbutanal, and 43.2 g of colorless transparent liquid of 4-(2,6,6-trimethyl-1-cyclohexenyl)-2-methylbutanal is obtained. The yield of 4-(2,6,6-trimethyl-1-cyclohexenyl)-2-methylbutanal is 96%. Among them, the top temperature of the hydrogenation kettle during the rough distillation process is 100 °C, and the kettle temperature of the hydrogenation kettle is 120 °C.

[0048] 12.4 g of malonic acid was divided into three parts, namely 2 g of the first malonic acid, 4 g of the second malonic acid, and 6.4 g of the third malonic acid. Under the protection of nitrogen, 20 g of 4-(2,6,6-trimethyl-1-cyclohexenyl)-2-methylbutyraldehyde, 1.12 g of the amino acid catalyst L-proline, 2 g of the first malonic acid, 24 mL of the second organic solvent cyclohexane, and 16 mL of the first water scavenger tert-butanol were added to a 1 L three-necked flask for a condensation reaction. When the reaction proceeded for 0.5 h, 4 g of the second malonic acid was added, and when the reaction proceeded for 1 h, 6.4 g of the third malonic acid was added. The temperature of the first oil bath was set at 80 °C, and the first reflux was for 3 h. Cyclohexane and tert-butanol were removed by vacuum distillation to obtain the first reaction solution. After the temperature of the first reaction solution dropped to room temperature, 50 g of the third organic solvent N-methylpyrrolidone and 4.6 g of the second water scavenger anhydrous magnesium chloride were continuously added for a decarboxylation reaction. The temperature of the second oil bath was set at 80 °C, and the second reflux was for 3 h to obtain the decarboxylated reaction solution. After the decarboxylated reaction solution was cooled to room temperature, it was neutralized with dilute hydrochloric acid aqueous solution, washed with water, subjected to the first extraction and the first vacuum concentration using cyclohexane, and yellow oil was obtained through vacuum distillation. The first recrystallization was carried out in n-hexane to obtain 11.6 g of white solid (E)-β-monocyclic homofarnesic acid, and the yield of (E)-β-monocyclic homofarnesic acid was 58%.

[0049] (E)-β-monocyclic homofarnesic acid was repeatedly prepared according to the above method. Finally, 25 g of (E)-β-monocyclic homofarnesic acid was dispersed in 100 g of the fourth organic solvent dichloromethane to obtain an (E)-β-monocyclic homofarnesic acid solution. 205 g of trifluoroacetic acid was dispersed in 200 g of the fifth organic solvent dichloromethane to obtain a trifluoroacetic acid catalyst trifluoroacetic acid solution. The (E)-β-monocyclic homofarnesic acid solution was slowly added dropwise to the trifluoroacetic acid solution. After the addition was completed, a cyclization reaction was carried out for 2 h to obtain the second reaction solution. The temperature of the second reaction solution was 0 °C. The second reaction solution was poured into ice water, and the second extraction was carried out using dichloromethane and the organic phase was collected. The organic phase was washed with sodium bicarbonate solution and deionized water until neutral, and then the second vacuum concentration was carried out. The second recrystallization was carried out in n-hexane to obtain 15 g of sclareolide reactant. Among them, in terms of mass percentage, the sclareolide reactant contained 60% of sclareolide with configuration (a), 30% of sclareolide with configuration (b), and 10% of sclareolide with configuration (c), and the yield of the sclareolide reactant was 60%.

[0050] Weigh 10 g of the sclareolide reactant and dissolve it in 100 g of the first organic solvent ethanol. Then add the first catalyst, where the first catalyst is 0.5 g of the Lewis base NaOH and 0.1 g of the inorganic salt NaCl. Heat up to 90 °C and then reflux. Stir at 300 rpm for 1 h for the configuration conversion reaction. The reaction pressure of the configuration conversion reaction is 1 atm. After the reaction is completed, through separation, purification, and crystallization, 8.90 g of the sclareolide product with a mass content of 99.2% in configuration (c) is obtained.

[0051] Example 2

[0052] The difference from Example 1 is that 100 g of the sclareolide reactant is dissolved in 800 g of the first organic solvent ethanol. Then add 5 g of the Lewis base NaOH and 1 g of the inorganic salt KCl. Heat up to 90 °C and then reflux. Stir at 500 rpm for 2 h for the configuration conversion reaction. After the reaction is completed, through separation, purification, and crystallization, 85.0 g of the sclareolide product with a mass content of 99.1% in configuration (c) is obtained.

[0053] Example 3

[0054] The difference from Example 1 is that, by mass percentage, the sclareolide reactant contains 50% of sclareolide in configuration (a), 40% of sclareolide in configuration (b), and 10% of sclareolide in configuration (c). Finally, 9.1 g of the sclareolide product with a mass content of 99.2% in configuration (c) is obtained.

[0055] Example 4

[0056] The difference from Example 2 is that, by mass percentage, the sclareolide reactant contains 50% of sclareolide in configuration (a), 40% of sclareolide in configuration (b), and 10% of sclareolide in configuration (c). Finally, 89.0 g of the sclareolide product with a mass content of 99.1% in configuration (c) is obtained.

[0057] Example 5

[0058] The difference from Example 1 is that the total mass of the Lewis base NaOH and the inorganic salt NaCl in the first catalyst is 0.6 g, and the mass ratio of the Lewis base NaOH to the inorganic salt NaCl is 5:1. Finally, 8.8 g of the sclareolide product with a mass content of 99.2% in configuration (c) is obtained.

[0059] Example 6

[0060] The difference from Example 1 is that the first catalyst is 0.6 g of the Lewis base NaOH. Finally, 7.5 g of the sclareolide product with a mass content of 99.3% in configuration (c) is obtained.

[0061] Example 7

[0062] The difference from Example 1 is that the mass ratio of the first catalyst to the sclareolide reactant is 10:100, and finally 9.1 g of sclareolide product with a mass content of 99.3% in configuration (c) is obtained.

[0063] Example 8

[0064] The difference from Example 1 is that the mass ratio of the first catalyst to the sclareolide reactant is 15:100, and finally 8.5 g of sclareolide product with a mass content of 99.2% in configuration (c) is obtained.

[0065] Example 9

[0066] The difference from Example 1 is that the reaction temperature of the configuration conversion reaction is 80 °C, the reaction pressure of the configuration conversion reaction is 30 atm, and finally 8.8 g of sclareolide product with a mass content of 99.2% in configuration (c) is obtained.

[0067] Example 10

[0068] The difference from Example 1 is that the reaction temperature of the configuration conversion reaction is 65 °C, the reaction pressure of the configuration conversion reaction is 35 atm, and finally 8.3 g of sclareolide product with a mass content of 99.0% in configuration (c) is obtained.

[0069] Example 11

[0070] The difference from Example 1 is that 12.4 g of malonic acid is added all at once, 6.1 g of white solid of (E)-β-monocyclic homofarnesoic acid is obtained, the yield of (E)-β-monocyclic homofarnesoic acid is 30.5%, and finally 8.9 g of sclareolide product with a mass content of 99.2% in configuration (c) is obtained.

[0071] Example 12

[0072] The difference from Example 1 is that the mass ratio of the sclareolide reactant to the first organic solvent ethanol is 1:50, and finally 9.3 g of sclareolide product with a mass content of 99.2% in configuration (c) is obtained.

[0073] Example 13

[0074] The difference from Example 1 is that the mass ratio of the sclareolide reactant to the first organic solvent ethanol is 1:55, and finally 8.9 g of sclareolide product with a mass content of 99.0% in configuration (c) is obtained.

[0075] Comparative Example 1

[0076] It is different from Example 2 in that 100 g of the sclareolide reactant is weighed and dissolved in 800 g of the first organic solvent ethanol, and then 80 mL of concentrated sulfuric acid with a mass concentration of 95% is added. After heating to 90 °C, reflux is carried out, and stirring is carried out at 300 rpm for 1 h for the configuration conversion reaction. After the reaction is completed, separation, purification and crystallization are carried out to obtain 68.1 g of the sclareolide product with a mass content of 99.2% in configuration (c).

[0077] Test method:

[0078] Yield of 4-(2,6,6-trimethyl-1-cyclohexenyl)-2-methylbutyraldehyde = mass of 4-(2,6,6-trimethyl-1-cyclohexenyl)-2-methylbutyraldehyde / α,β-unsaturated 4-(2,6,6-trimethyl-1-cyclohexenyl)-2-methylbutenal.

[0079] (E)-β-monocyclic homofarnesoic acid yield = mass of (E)-β-monocyclic homofarnesoic acid / 4-(2,6,6-trimethyl-1-cyclohexenyl)-2-methylbutyraldehyde.

[0080] Yield of sclareolide reactant = mass of sclareolide reactant / mass of (E)-β-monocyclic homofarnesoic acid.

[0081] Yield of sclareolide product in configuration (c) = mass of sclareolide in configuration (c) / mass of sclareolide reactant.

[0082] Testing the mass contents of sclareolide in configuration (a), sclareolide in configuration (b) and sclareolide in configuration (c) in the sclareolide reactant: Test by gas chromatography.

[0083] The yield results of the sclareolide products in configuration (c) of the above examples and comparative examples are shown in Table 1.

[0084] Table 1

[0085]

[0086]

[0087] Among them, Figure 1 is the synthesis reaction path diagram of sclareolide in configuration (c). As can be seen from Figure 1 , α,β-unsaturated 4-(2,6,6-trimethyl-1-cyclohexenyl)-2-methylbutenal successively undergoes hydrogenation reaction, condensation reaction, decarboxylation reaction and cyclization reaction to obtain sclareolide reactants including those containing configuration (a) and configuration (b). The sclareolide in configuration (a) and configuration (b) undergoes a configuration conversion reaction to obtain sclareolide in configuration (c).

[0088] From the above description, it can be seen that the above embodiments of the present invention achieve the following technical effects:

[0089] Compared with the addition of an acidic reagent in the sclareolide transposition method, the acidic reagent will be further transposed into other isomers. In this application, a commonly available and easily obtained Lewis base is used as a catalyst to carry out a configuration conversion reaction on sclareolide of configuration (a) and sclareolide of configuration (b) to obtain sclareolide of configuration (c). This transposition method has higher selectivity for sclareolide of configuration (c), thereby increasing the yield of sclareolide of configuration (c). In addition, the transposition method of this application has the advantages of high conversion rate, short reaction time, high product yield, low product cost, no environmental pollution, and simple post-treatment.

[0090] The above are only the embodiments of the present invention and are not intended to limit the present invention. For those skilled in the art, the present invention can have various modifications and changes. Any modifications, equivalent replacements, improvements, etc. made within the spirit and principle of the present invention shall be included within the protection scope of the present invention.

Claims

1. A method for translocation of sclareolide, characterized in that: The transposition method comprises: A raw material including a sclareolide reactant and a first catalyst is subjected to a configuration conversion reaction to obtain a sclareolide product of configuration (c); wherein the sclareolide reactant includes sclareolide of configuration (a) and / or sclareolide of configuration (b); The chemical structures of the sclareolide of configuration (a), the sclareolide of configuration (b), and the sclareolide of configuration (c) are respectively: The first catalyst comprises a Lewis base.

2. The indexing method according to claim 1, characterized in that: The Lewis base is selected from any one or more of LiOH, NaOH, KOH, Na2CO3 and NaHCO3; and / or, the first catalyst also includes an inorganic salt, the mass ratio of the Lewis base to the inorganic salt is 5 to 10:1, and the inorganic salt is NaCl and / or KCl; and / or, the mass ratio of the first catalyst to the clary sclarea lactone reactant is 1 to 10:

100.

3. The indexing method according to claim 1 or 2, characterized in that: The raw material further includes a first organic solvent, the first organic solvent is selected from any one or more of ethanol, propylene glycol and toluene; and / or the mass ratio of the sclareolide reactant to the first organic solvent is 1:5-50; And / or, the reaction temperature of the configuration conversion reaction is 70-90° C., and / or, the reaction pressure of the configuration conversion reaction is 1-30 atm, and / or, the reaction time of the configuration conversion reaction is 1-5 hours.

4. The indexing method according to any one of claims 1 to 3, characterized in that: The preparation method of the sclareolide reactant comprises: Step S1, sequentially subjecting raw materials including α,β-unsaturated 4-(2,6,6-trimethyl-1-cyclohexene)-2-methylbutenal, a palladium-carbon catalyst and a sodium hydroxide solution to a first mixing, a hydrogenation reaction and a rough distillation to obtain 4-(2,6,6-trimethyl-1-cyclohexene)-2-methylbutanal; Step S2, sequentially subjecting the raw materials including the 4-(2,6,6-trimethyl-1-cyclohexene)-2-methylbutanal, malonic acid and an amino acid catalyst to a condensation reaction and a decarboxylation reaction to obtain (E)-β-monocyclic homoacacic acid; Step S3, subjecting the raw materials including the (E)-β-monocyclic homoacacic acid and trifluoroacetic acid catalyst to a cyclization reaction to obtain the sclareolide reactant.

5. The indexing method according to claim 4, characterized in that: In the step S1, the palladium-carbon catalyst is a 3-5wt% Pd / C catalyst, the mass ratio of the α,β-unsaturated 4-(2,6,6-trimethyl-1-cyclohexene)-2-methylbutenal to the palladium-carbon catalyst is 90-110:1; and / or the mass ratio of sodium hydroxide to water in the sodium hydroxide solution is 1-3:

100.

6. The indexing method according to claim 4, characterized in that: The step S1 further comprises: performing the hydrogenation reaction and the rough distillation on the first mixed liquid after the first mixing by using a hydrogenation kettle for gas replacement; wherein nitrogen and hydrogen are used for the gas replacement, and the number of gas replacements is 3 to 5 times; And / or, during the crude steaming process, the top temperature of the hydrogenation kettle is 100-105° C., and the kettle temperature of the hydrogenation kettle is 120-130° C.; And / or, the reaction temperature of the hydrogenation reaction is 60-80° C., the reaction pressure of the hydrogenation reaction is 2.5-3.0 MPa, and the reaction time of the hydrogenation reaction is 3-5 h.

7. The indexing method according to claim 4, characterized in that: The step S2 further comprises: Step S21, performing the condensation reaction on the raw materials including the 4-(2,6,6-trimethyl-1-cyclohexene)-2-methylbutanal, the malonic acid, the amino acid catalyst, the second organic solvent and the first dehydrating agent, followed by reduced pressure distillation to obtain a first reaction solution; Step S22, after subjecting the raw material including the first reaction solution, the third organic solvent and the second dehydrating agent to the decarboxylation reaction, sequentially performing a first washing, a first extraction, a first reduced pressure concentration and a first recrystallization to obtain (E)-β-monocyclic homoacacic acid; Among them, the malonic acid is added to the condensation reaction in the form of the first malonic acid, the second malonic acid and the third alanine in sequence, the sum of the total masses of the first malonic acid, the second malonic acid and the third alanine is equal to the mass of the malonic acid, and the mass ratio of the first malonic acid, the second malonic acid and the third alanine is 1:1~3:3~5.

8. The indexing method according to claim 7, characterized in that: The amino acid catalyst is L-proline, the second organic solvent is cyclohexane, and the first water removal agent is tert-butanol; And / or, the mass ratio of the 4-(2,6,6-trimethyl-1-cyclohexene)-2-methylbutanal, the malonic acid and the amino acid catalyst is 20-25:12.4-15:1.12-1.5; the mass ratio of the 4-(2,6,6-trimethyl-1-cyclohexene)-2-methylbutanal to the volume of the first water removal agent is 1.25-1.5 g / mL; And / or, the reaction temperature of the condensation reaction and the decarboxylation reaction is independently 80-85° C., and the reaction time of the condensation reaction and the decarboxylation reaction is independently 3-4 h; And / or, the third organic solvent is N-methylpyrrolidone, and the second water removing agent is magnesium chloride; And / or, the mass ratio of the first reaction liquid to the second dehydrating agent is 100-110:20-25.

9. The indexing method according to claim 4, characterized in that: The step S3 further comprises: Step S31, mixing the (E)-β-monocyclic homoacacic acid and a fourth organic solvent to obtain a (E)-β-monocyclic homoacacic acid solution; Step S32, mixing the trifluoroacetic acid and a fifth organic solvent to obtain a trifluoroacetic acid solution; Step S33, subjecting the (E)-β-monocyclic homoacacic acid solution and the trifluoroacetic acid solution to the cyclization reaction to obtain a second reaction solution; Step S34, subjecting the second reaction liquid to a second extraction, a second washing, a second reduced pressure concentration and a second recrystallization in sequence to obtain the sclareolide reactant.

10. The indexing method according to claim 9, characterized in that: The fourth organic solvent and the fifth organic solvent are each independently dichloromethane; And / or, the mass ratio of the (E)-β-monocyclic homoacacic acid solution to the trifluoroacetic acid solution is 125-150:405-500; and / or, the temperature of the second reaction solution is -10-0°C; and / or, the reaction time of the cyclization reaction is 2-3h.

Images